Evaluation and validation of the increased annexin A3 (ANXA3) as a novel biomarker to predict sepsis in critically ill patients

Abstract Background: Current research indicated Annexin A3 (ANXA3) was involved in innate immunity. Nevertheless, the comprehensive expression of ANXA3 in sepsis patients remain uncertain.Methods: We performed a meta-analysis utilizing public datasets form Array Express and Gene Expression Omnibus (GEO) to summarize and evaluate the expression level of ANXA3 in sepsis patients. Then, we investigated the associations between plasma ANXA3 and sepsis via a retrospective study. The predictive ability of plasma ANXA3 for sepsis was evaluated using the Area Under the Curve (AUC).Results: Totally, the meta-analysis including 2612 sepsis and 2259 controls indicated sepsis patients were with markedly higher levels of ANXA3 mRNA expression (SMD=2.04 (1.54-2.55); p<0.00001). Meanwhile, sepsis deaths (n=500) were with limited higher expression of ANXA3 mRNA than sepsis survivors (n=1711) (SMD=0.11(0.01-0.22); p=0.03). Furthermore, our results indicated plasma ANXA3 on admission were significantly associated with the incidence of sepsis in critically ill patients (OR=2.41(1.75-3.32), p<0.001). As a predictive biomarker, plasma ANXA3 resulted in a better AUC 0.815(0.745-0.886) than procalcitonin (PCT) (0.673(0.584-0.761)) and interleukin-6 (IL-6) (0.672(0.585-0.759)) and SOFA score (0.668(0.577-0.759)). Additionally, patients with high plasma ANXA3 had a poorer overall 28-day survival in critically ill patients (HR=2.16(1.09-4.28); p=0.028), but not for sepsis patients (HR=1.63(0.65-4.06); p=0.276).Conclusions: This study evaluated and validated ANXA3 was increased in sepsis. As a predictive biomarker, plasma ANXA3 obtained a good predictive ability for sepsis. Meanwhile, plasma ANXA3 was associated with outcomes of critically ill patients, but not sepsis patients.